The long-term goal of our research is to elucidate underlying mechanisms by which the physical and social environments result in health disparities. Our previous work has shown that the hypothesis that lead exposure is a risk factor for dental caries is plausible and could have significant public health impact, especially for individuals in impoverished circumstances (Watson et al., 1997; Moss et al., 1999). We will study dental caries risk due to environmental lead exposure in a birth cohort of 245 Cincinnati children that have been participants in the Cincinnati Lead Cohort Study since late 1979. The on-going study of 15-16 year-olds is currently in its third year of funding (R01 ES08158, Early Exposure to Lead and Adolescent Development, P.I.: K. Dietrich). This group of African-American and white Appalachian children is arguably the most well-described longitudinal cohort ever studied for prenatal and postnatal lead exposure (prenatal maternal blood lead concentration, neonatal blood lead concentration, quarterly assessments of the concentration of lead in blood from birth to 5 years and semi-annually thereafter). This cohort is unique among the major longitudinal studies of lead and child health in that a substantial number of subjects were exposed to clinically significant levels of lead during early development. Peak lead exposure in this cohort ranges from 5 to over 80 micrograms/dL. We will collect additional data specifically related to dental caries risk and perform laboratory microanalytic assessments of lead in plaque and enamel. This will allow us to test a series of hypotheses that relate environmental lead exposure to risk for dental caries development in adolescents. The work of this project will focus on four specific aims related to 1) Demonstrating the strength of the association between environmental lead exposure and risk for dental caries and ruling out alternative explanations; 2) Assessing the utility of permanent tooth enamel, deciduous tooth enamel, deciduous tooth dentin and supragingival plaque as biomarkers for lead exposure using microanalytic techniques; 3) Testing mechanistic hypotheses that show lead exposure a) reduces salivary gland function; b) acts as an effect modifer to reduce the protective effect of salivary fluoride; c) is most strongly linked to caries when measured during enamel formation; 4) Exploring more broadly the basis for oral disease disparities in disadvantaged groups by examining the interplay of lead, nutrition, and social factors.